Journal article
Human newborn bacille Calmette–Guérin vaccination and risk of tuberculosis disease: a case-control study
- Abstract:
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Background
An incomplete understanding of the immunological mechanisms underlying protection against tuberculosis (TB) hampers the development of new vaccines against TB. We aimed to define host correlates of prospective risk of TB disease following bacille Calmette–Guérin (BCG) vaccination.
Methods
In this study, 5,726 infants vaccinated with BCG at birth were enrolled. Host responses in blood collected at 10 weeks of age were compared between infants who developed pulmonary TB disease during 2 years of follow-up (cases) and those who remained healthy (controls).
Results
Comprehensive gene expression and cellular and soluble marker analysis failed to identify a correlate of risk. We showed that distinct host responses after BCG vaccination may be the reason: two major clusters of gene expression, with different myeloid and lymphoid activation and inflammatory patterns, were evident when all infants were examined together. Cases from each cluster demonstrated distinct patterns of gene expression, which were confirmed by cellular assays.
Conclusions
Distinct patterns of host responses to Mycobacterium bovis BCG suggest that novel TB vaccines may also elicit distinct patterns of host responses. This diversity should be considered in future TB vaccine development.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
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- Files:
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(Preview, Version of record, pdf, 3.2MB, Terms of use)
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- Publisher copy:
- 10.1186/s12916-016-0617-3
Authors
Contributors
- Institution:
- University of Oxford
- Division:
- MSD
- Department:
- NDM
- Sub department:
- Jenner Institute
- Role:
- Contributor
- Grant:
- NF-SI-0514-10158
- NF-SI-0509-10233
- Publisher:
- BioMed Central
- Journal:
- BMC Medicine More from this journal
- Volume:
- 14
- Issue:
- 1
- Pages:
- 76
- Publication date:
- 2016-05-16
- Acceptance date:
- 2016-04-23
- DOI:
- EISSN:
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1741-7015
- Pmid:
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27183822
- Language:
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English
- Keywords:
- Pubs id:
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pubs:708378
- UUID:
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uuid:ca024b02-1d1b-4e0b-a9d7-f935669fe3a7
- Local pid:
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pubs:708378
- Source identifiers:
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708378
- Deposit date:
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2019-07-03
Terms of use
- Copyright holder:
- Fletcher et al
- Copyright date:
- 2016
- Notes:
- © 2016 Fletcher et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Licence:
- CC Attribution (CC BY)
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